This investigation represents an alternative approach to the development of synthetic, non-thombogenic surfaces. The active and complex metabolic processes of the endothelial cell, the only known non-thrombogenic surface, mitigate against discovery of truly non-thrombogenic, synthetic materials. Alternatively, we seek to determine which elements of the hemostatic system are directly activated by contact with synthetic surfaces, and then to discover inhibitors that prevent activation of these elements. We will study fresh heparinized or citrated human blood in an in vitro extracorporeal perfusion circuit containing a membrane or bubble oxygenator, and also make measurements on patients who have mechanical cardiac valves, or who undergo open heart surgery. We will measure changes in factor XI, C1-inhibitor, prekallikrein and high molecular weight kninogen (HMWK) with 3 amidolytic assays and 1 clotting assay. We will also measure enzyme-inhibitor complexes, kallikrein-C1-INH and factor XIIa-C1-INH with monospecific polyclonal antibodies, and will develop assays to kallikrein-C1-INH and HMWK using monocloncal antibodies. We weill also study 3 patients with cogenital deficiencies of contact coagulation proteins and extract, and purify and test corn trypsin inhibitor (to factor XIIa). These studies should determine the sites of surface activation of the contact coagulation proteins. We will also study surface activation of leukocytes and platelets. Changes in leukocyte function, complement activation, and release of acid hydrolases, elastase and lactoferrin, will be measured in vitro and in vivo. We will study release of leukocyte thromboplastin-like procoagulant material caused by blood-surface contact in vitro and in vivo. We will measure changes in ADP receptors, and platelet membrane glycoprotein IIb/IIIa complexes to determine whether or not surface contact causes fragmentation of platelet membranes. We will also measure release in vitro and in vivo of platelet specific markers-glycocalicin, LA-PF4 and thrombospondin, and determine whether or not platelets can bind factor V after surface contact. Selective inhibition of surface-activated coagulants may increase applications of extracorporeal perfusion technology and intravascular devices and decrease associated bleeding and thromboembolic complications.